PubMed Health⌕ Search

Biomedical subjects

N Rothman

Publications and source records attributed to N Rothman.

115 records · Page 7Linked to original sources
PubMedDate not supplied

Quantitation of DNA in buccal cell samples collected in epidemiological studies.

Buccal cell samples are increasingly used in epidemiological studies as a source of genomic DNA. The accurate and precise quantitation of human DNA is critical for the optimal use of these samples. However, it is complicated by the presence of bacterial DNA and wide inter-individual variation in DNA concentration from buccal cell collections. The paper evaluated the use of ultraviolet light (UV) spectroscopy, Höechst (H33258) and PicoGreen as measures of total DNA, and real-time quantitative polymerase chain reaction (PCR) as a measure of human amplifiable DNA in buccal samples. Using serially diluted white blood cell DNA samples (at a concentration range of 300 to 0.5 ng microl-1), UV spectroscopy showed the largest bias, followed by Höechst, especially for low concentrations. PicoGreen and real-time PCR provided the most accurate and precise estimates across the range of concentrations evaluated, although an increase in bias with decreasing concentrations was observed. The ratio of real-time PCR to PicoGreen provided a reasonable estimate of the percentage of human DNA in samples containing known mixtures of human and bacterial DNA. Quantification of buccal DNA from samples collected in a breast cancer case-control study by PicoGreen and real-time PCR indicated that cytobrush and mouthwash DNA samples contain similar percentages of human amplifiable DNA. Real-time PCR is recommended for the quantification of buccal cell DNA in epidemiological studies since it provides precise estimates of human amplifiable DNA across the wide range of DNA concentrations commonly observed in buccal cell DNA samples.

Cheek↗
PubMedDate not supplied

The carcinogenic potential of selected petroleum-derived products.

In this chapter the authors examine the toxicologic and epidemiologic literature for a broad range of petroleum-derived products in order to assess the carcinogenic potential of these compounds. Types of evidence used, classes of compounds, and qualitative assessments of carcinogenicity are presented.

Animals↗
PubMedDate not supplied

No point mutation but a codon 31ser-->arg polymorphism of the WAF-1/CIP-1/p21 tumor suppressor gene in nasopharyngeal carcinoma (NPC): the polymorphism distinguishes Caucasians from Chinese.

Mutational inactivation of the p53 tumor suppressor gene is an infrequent event in human nasopharyngeal carcinoma (NPC), a malignancy showing a high incidence in southern China and southeast Asia. To examine the possible involvement of an activated p53 pathway in nasopharynx carcinogenesis, we have screened primary NPC biopsies for possible point mutations in WAF-1/CIP-1/p21, an effector gene transcriptionally regulated by and functioning as a mediator of the p53 tumor suppressor gene. Mutations in WAF-1/CIP-1/p21 might mimic p53 mutations in tumors having wild-type p53 such as most NPCs. The mutational analysis of WAF/CIP/p21 by PCR-single strand conformational polymorphism-direct sequencing revealed no point mutation in 41 primary NPC biopsies. A codon 31ser-->arg polymorphism was, however, detected. A striking difference in the distribution of the serine (WAF-ser) and arginine (WAF-arg) forms of WAF-1/CIP-1/p21 was observed when normal healthy Caucasians and Chinese were compared (P < 0.0001). The majority of Caucasians examined were found to be homozygous for WAF-ser (89%, n = 65), while Chinese living in areas of high NPC incidence show a greater than 86% homozygous or heterozygous WAF-arg (Taiwan, n = 66; Hunan, n = 32). The two forms of WAF-1/CIP-1/p21 were examined for potential functional differences in their ability to inhibit cyclin-dependent kinases and tumor cell growth. No significant differences were detected. Furthermore, no association between WAF-1/CIP-1/p21 genotype and NPC risk was observed in a case-control study of 76 NPC cases and 66 normal controls conducted in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Misclassification of genetic susceptibility biomarkers: implications for case-control studies and cross-population comparisons.

Phenotype and genotype markers of genetic susceptibility are of increasing interest in case-control studies of cancer. It is well established that bias to the odds ratio is caused by less-than-perfect assay sensitivity and specificity and varies with risk factor prevalence. As such, the observed variation in odds ratio between studies of genetic markers and cancer risk may be real, or may be attributed, in part, to variation in assay accuracy or in risk factor prevalence (e.g., prevalence differences between racial groups). The latter can be a particular concern when the prevalence of the "at risk" polymorphism in one or more populations is either very high (e.g., > 85%) or very low (e.g., < 15%). For example, even very high sensitivity (e.g., 98%) can produce substantial bias to the odds ratio when the risk factor prevalence is high. Under some prevalence conditions, however, assays with only moderate accuracy are sufficient and result in minimal bias to the odds ratio. Understanding misclassification in the context of marker prevalence may help to explain disparate findings in the literature and should assist investigators in selecting markers that are appropriate for future studies.

Bias↗
PubMedDate not supplied

Contribution of occupation and diet to white blood cell polycyclic aromatic hydrocarbon-DNA adducts in wildland firefighters.

Wildland (forest) firefighters are exposed to a wide range of carcinogenic polycyclic aromatic hydrocarbons (PAH) in forest fire smoke. PAH undergo metabolic activation and can subsequently bind to DNA. In this study, we investigated the association between occupational and dietary PAH exposures and the formation of WBC PAH-DNA adducts in a population of wildland firefighters. An enzyme-linked immunosorbent assay using an antiserum elicited against benzo(a)pyrene-modified DNA was used to measure PAH-DNA adducts in WBC obtained from 47 California firefighters at two time points, early and late in the 1988 forest fire season. PAH-DNA adduct levels were not associated with cumulative hours of recent firefighting activity. However, firefighters who consumed charbroiled food within the previous week had elevated PAH-DNA adduct levels, which were related to frequency of charbroiled food intake. These findings suggest that dietary sources of PAH contribute to PAH-DNA adduct levels in peripheral WBC and should be evaluated when using this assay to assess occupational and environmental PAH exposure.

Adolescent↗
PubMedDate not supplied

Respiratory health hazards and lung function in wildland firefighters.

The authors discuss the multitude of contaminants to which wildland firefighters are exposed, including carbon monoxide, sulfur dioxide, particulate and silica, polyaromatic hydrocarbons, aldehydes, and benzene. They examine the respiratory effects of these contaminants and then present their recommendations for an occupational health program for wildland firefighters.

Environmental Monitoring↗